Background: The NCI-MATCH precision medicine trial assigns patients (pts) with solid tumors, lymphoma, or multiple myeloma whose cancers have progressed on prior treatment to a targeted therapy based on genetic alterations identified in pre-treatment biopsies. Arm K2 (EAY131-K2) evaluated the pan-FGFR inhibitor erdafitinib (E) in pts with FGFR mutations or fusions. Patients and methods: Pts with bladder or urothelial cancers were excluded. Pts received E 8 mg PO daily (28-day cycle) until disease progression or unacceptable toxicity; dose reduction for toxicities was allowed; imaging was performed every 2 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: A total of 35 pts were enrolled to this arm from 07/2018-07/2019; one was ineligible and one did not receive treatment. Nine distinct tumor histologies were represented, most common being pancreatobiliary (11), CNS (7) and gynecological tumors (5). 73% of pts were female, with median age of 59y (range 26-83y), 70% were Caucasian, and 61% of pts had received at least 3 prior therapies (range 0-22). Alterations in FGFR1, FGFR2 and FGFR3 were recorded in 6, 18, and 9 evaluable pts, respectively. 18 pt tumors had fusions and 15 had mutations in an FGFR gene. The confirmed ORR was 12% (90% CI 4%, 26%), with a median duration of response (DoR) of 7.3 months (mo), range 4.2-11.7 mo. Responses were seen in cholangiocarcinoma (2 pts), Brenner ovarian tumor and adenoid cystic carcinoma (1 pt each). Two (50%) of these 4 tumors harbored FGFR fusions and 2 FGFR mutations. 13 pts had stable disease (SD). Median PFS was 3.9 mo, and 6-mo PFS was 32.8% (90% CI 21.2%, 50.6%). Median OS was 11.0 mo. Of the 6 pts with intrahepatic cholangiocarcinoma, 2 had PR and 2 SD. The most frequent grade 3 treatment-related AEs were oral mucositis/pain (5 pts), paronychia, electrolyte disorders, and anemia/lymphopenia (2 pts each). There were no treatment-related grade 4-5 toxicities. Toxicities were reversible and manageable with E dose interruptions and/or dose reduction. Conclusions: In this pre-treated, mixed histology cohort with tumors harboring FGFR somatic alterations, E showed activity with durable responses and disease stabilizations outside of currently approved FDA indications, although the pre-specified criterion that the primary endpoint, ORR, be significantly greater than 16% was not reached. Toxicities were consistent with E safety profile. Responses were observed in tumors harboring FGFR fusions as well as in those with mutations of FGFR; further correlative analyses are planned.

Citation Format: Alain C Mita, Zihan Wei, Ingrid A Mayer, Heather Cheng, Edith P Mitchell, John J Wright, Percy Ivy, Robert J Gray, Victoria Wang, Lisa M McShane, Larry V Rubinstein, David R Patton, Mickey Williams, Stanley R Hamilton, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty. Erdafitinib in patients with tumors harboring FGFR gene mutations or fusions: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Sub-protocol K2 [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA003.